tbuckley/cabot-search huggingface dataset:
Cardiac Involvement in a Large Kindred With Myotonic Dystrophy
Authors: Lale S. Tokgozoglu
Journal: JAMA (1995)

<h3>Objective.</h3> —To evaluate and quantitate cardiac involvement in myotonic dystrophy and assess whether the size of the trinucleotide (cytosine-thymine-guanine [CTG]) repeat expansion is a significant predictor of cardiac abnormalities. <h3>Design.</h3> —Case-control study of a large kindred with myotonic dystrophy. <h3>Patients.</h3> —Ninety-one bloodline members of the kindred underwent clinical and cardiac evaluation with electrocardiograms, echocardiography (with Doppler in the majority of cases), and genetic and neurologic evaluations. Affected individuals were age-matched to normal family members. <h3>Main Outcome Measures.</h3> —Electrocardiographic conduction abnormalities, wall motion abnormalities, mitral valve prolapse, and global parameters of systolic and diastolic function were determined by an observer blinded to all clinical data and genetic analysis. <h3>Results.</h3> —Compared with age-matched normals, patients with myotonic dystrophy (n=25) were more likely to have conduction abnormality (52% vs 9%), mitral valve prolapse (32% vs 9%), and wall motion abnormality (28% vs 0%) (all<i>P</i>&lt;.05). Left ventricular ejection fraction and stroke volume were reduced compared with normals matched for age and heart rate (<i>P</i>&lt;.05), whereas Doppler indexes of diastolic function were only marginally altered. Using multivariate analysis, the number of CTG repeats (range, 69 to 1367; normal, ≤37) was the strongest predictor of abnormalities in wall motion and electrocardiographic conduction (odds ratio of 16.5 and 5.07 per 500 repeats, respectively). The relation of mitral valve prolapse to the size of the CTG repeat was of borderline significance. Patients with more extensive neurologic findings (n=12) had a higher incidence of wall motion and/or electrocardiographic conduction abnormalities (83% vs 43%;<i>P</i>=.04). <h3>Conclusions.</h3> —Cardiac involvement in myotonic dystrophy affects predominantly the conduction system and myocardial function. Alterations in myocardial relaxation and diastolic properties, in contrast to skeletal muscle myotonia, are minor. In this kindred, the number of CTG repeats was a significant predictor of cardiac dysfunction in myotonic dystrophy. (<i>JAMA</i>. 1995;274:813-819)
Candida parapsilosis Endocarditis
Authors: Robert D. Brandstetter
Journal: JAMA (1980)

ENDOCARDITIS due to bacterial and fungal pathogens is a special problem in the addict population, with more than 20% of fungal endocarditis being associated with drug addiction.<sup>1</sup>It has been postulated that intravenous (IV) injections of adulterated substances, such as illicit heroin, can cause fibrotic changes in cardiac valves predisposing to subsequent microbial endocarditis; however, the source of the pathogen has not been elucidated in these infections.<sup>2</sup>We report here a case of<i>Candida parapsilosis</i>endocarditis in which the infecting organism was cultured from the patient's injection paraphernalia. <h3>Report of a Case</h3> A 24-year-old male drug addict was admitted with a one-week history of fever, weakness, fatigue, and arthralgias. He gave a history of heroin addiction for eight years, and he had had<i>Staphylococcus aureus</i>endocarditis requiring aortic valve replacement five years before this admission. On five occasions during the preceding three months, and most recently two weeks
Life Expectancy With Atrial Septal Defect
Authors: James E. Dalen
Journal: JAMA (1967)

Of 48 patients with secundum atrial septal defects diagnosed by cardiac catheterization from 1945 to 1956, 29 (60%) were still alive in 1966. Survival was markedly influenced by the presence of complicating pulmonary vascular disease. Twenty-one of 23 patients with normal pulmonary vascular resistance were still alive in 1966. However, only five of 20 patients with pulmonary vascular disease were alive (average age, 50). Six of these 20 patients died at surgery, and nine of their heart disease (average age, 41). Catheterization during the follow-up period showed that severe pulmonary vascular disease had developed in two patients. The impossibility of predicting in which patients severe pulmonary vascular disease will develop, combined with the prohibitive surgical risk that it presents, suggests that all atrial defects without pulmonary vascular disease should be surgically corrected.
The Physician's Responsibility for Suicide. I. An Error of Commission
Authors: GEORGE E. MURPHY
Journal: Annals of Internal Medicine (1975)

A series of individuals who committed suicide by overdose of medication was matched for age, sex, and marital status with individuals who committed suicide by other means in the same time period. Somewhat more of those who died by overdose had been under the recent care of a physician (91% versus 71%). Over half of those who died by overdose had received a prescription within a week or less before dying or had an unlimited prescription for a fully lethal amount of the hypnotic substance ingested. Individuals receiving smaller prescriptions (less than a total of 1.5 g secobarbital or the equivalent) either augmented this supply with other medications available or used something else entirely. Thus, in over half the cases, the physician supplied the complete means for suicide in a single prescription. The availability of a recently prescribed lethal amount of medication strikingly distinguished the ingesters from the noningester controls.
Percutaneous Transluminal Coronary Angioplasty in New York State
Authors: Edward L. Hannan
Journal: JAMA (1992)

<h3>Objective.</h3> —To identify significant independent risk factors for major percutaneous transluminal coronary angioplasty outcomes. <h3>Design.</h3> —Retrospective analysis using univariate and logistic regression analysis to identify significant independent risk factors for adverse outcomes. <h3>Setting.</h3> —All 31 hospitals performing percutaneous transluminal coronary angioplasty in New York State in 1991. <h3>Patients.</h3> —All 5827 patients undergoing percutaneous transluminal coronary angioplasty between January 1, 1991, and June 30, 1991, in New York State. <h3>Main Outcome Measures.</h3> —In-hospital mortality, major complication(s) (in-hospital mortality, myocardial infarction, and/or emergency coronary artery bypass graft), and absence of angiographic success (stenosis reduction of less than 20% on any attempted lesion or residual stenosis of at least 50% on any attempted lesion). <h3>Main Results.</h3> —Before discharge from the hospital, a total of 37 patients (0.63%) died; 67 patients (1.1%) suffered a myocardial infarction, with a mortality rate of 4.5%; and 97 patients (1.7%) underwent emergency coronary artery bypass graft surgery, with a mortality rate of 2.1% (no deaths in 85 patients who were hemodynamically stable and two deaths among 12 patients who were hemodynamically unstable). A total of 187 patients (3.2%) experienced a major complication. Angiographic success was achieved for 88% of all patients. Multivariate analysis found four independent preprocedural variables related to death: female gender, hemodynamic instability, shock, and ejection fraction. <h3>Conclusions.</h3> —Percutaneous transluminal coronary angioplasty outcomes in New York compare favorably with other recent results reported in the literature. Several preprocedural variables markedly increase the incidence of adverse events. (<i>JAMA</i>. 1992;268:3092-3097)
Differences in the Association Between Alcoholic Beverage Type and Serum Urate Levels Using Standardized Ethanol Content
Authors: Sho Fukui, Masato Okada, Mahbubur Rahman, Hiroki Matsui, Atsushi Shiraishi, Takehiro Nakai, Hiromichi Tamaki, Mitsumasa Kishimoto, Hiroshi Hasegawa, Takeaki Matsuda, Kazuki Yoshida
Journal: JAMA Network Open (2023)

Differences have been observed in the association of serum urate levels with consumption of different types of alcoholic beverages. However, previous studies have not standardized the unit of intake for ethanol content, and only limited types of alcoholic beverages have been evaluated.To examine differences in the association of serum urate levels with various types of alcoholic beverages when their intakes are standardized for ethanol content.This retrospective cross-sectional study was conducted using data from participants aged 20 years or older who completed a medical checkup at St Luke's International University in Japan between October 1, 2012, and October 31, 2021. Participant demographics, blood test results, and lifestyle questionnaire data were used as covariates. Analysis was performed in December 2021.Consumption of alcoholic beverages, including beer, sake (rice wine), shochu (Japanese spirit), wine, and whiskey.Serum urate levels were measured during the medical checkup. The beverage unit was standardized to 1 standard drink, which contained 20 g of ethanol. Multivariable linear regression including interaction terms of alcohol consumption and dominant alcoholic beverage was performed.This study included 78 153 participants. Their mean (SD) age was 47.6 (12.8) years; 36 463 (46.7%) were men and 41 690 were women (53.3%). A total of 45 755 participants (58.5%) were regular alcohol drinkers. Consistent associations of serum urate levels with alcohol consumption were observed in the beer-dominant group, with β coefficients (for 1 standard drink per day) of 0.14 mg/dL (95% CI, 0.11-0.17 mg/dL; P < .001) for men and 0.23 mg/dL (95% CI, 0.20-0.26 mg/dL; P < .001) for women. A moderate increase in serum urate levels was observed in the wine-dominant group compared with a modest and nonsignificant increase in the sake-dominant group, with β coefficients (for 1 standard drink per day) for the latter group of 0.05 mg/dL (95% CI, -0.01 to 0.10; P = .10) for men and 0.04 mg/dL (95% CI, -0.05 to 0.14 mg/dL; P = .38) for women. Restricted cubic splines showed different patterns in associations of serum urate levels with ethanol intake by dominant alcoholic beverages.The results of this study suggest that the extent of the association of serum urate levels with alcohol intake was different for alcoholic beverages even after ethanol content was standardized. Higher beer consumption among men and women was consistently associated with higher serum urate levels, whereas sake was not associated with changes in serum urate levels. Therefore, alcoholic beverage type, in addition to ethanol content, should be considered as a factor contributing to hyperuricemia.
Eye on genome editing
Authors: Samuel W. Du, Krzysztof Palczewski
Journal: The Journal of Experimental Medicine (2023)

CRISPR/Cas9 genome editing techniques have the potential to treat previously untreatable inherited genetic disorders of vision by correcting mutations that cause these afflictions. Using a prime editor, Qin et al. (2023. J. Exp. Med.https://doi.org/10.1084/jem.20220776) restored visual functions in a mouse model (rd10) of retinitis pigmentosa.
Automated prioritization of sick newborns for whole genome sequencing using clinical natural language processing and machine learning
Authors: Bennet Peterson, Edgar Javier Hernandez, Charlotte Hobbs, Sabrina Malone Jenkins, Barry Moore, Edwin Rosales, Samuel Zoucha, Erica Sanford, Matthew N. Bainbridge, Erwin Frise, Albert Oriol, Luca Brunelli, Stephen F. Kingsmore, Mark Yandell
Journal: Genome Medicine (2023)

Rapidly and efficiently identifying critically ill infants for whole genome sequencing (WGS) is a costly and challenging task currently performed by scarce, highly trained experts and is a major bottleneck for application of WGS in the NICU. There is a dire need for automated means to prioritize patients for WGS. Institutional databases of electronic health records (EHRs) are logical starting points for identifying patients with undiagnosed Mendelian diseases. We have developed automated means to prioritize patients for rapid and whole genome sequencing (rWGS and WGS) directly from clinical notes. Our approach combines a clinical natural language processing (CNLP) workflow with a machine learning-based prioritization tool named Mendelian Phenotype Search Engine (MPSE). MPSE accurately and robustly identified NICU patients selected for WGS by clinical experts from Rady Children's Hospital in San Diego (AUC 0.86) and the University of Utah (AUC 0.85). In addition to effectively identifying patients for WGS, MPSE scores also strongly prioritize diagnostic cases over non-diagnostic cases, with projected diagnostic yields exceeding 50% throughout the first and second quartiles of score-ranked patients. Our results indicate that an automated pipeline for selecting acutely ill infants in neonatal intensive care units (NICU) for WGS can meet or exceed diagnostic yields obtained through current selection procedures, which require time-consuming manual review of clinical notes and histories by specialized personnel.
Targeted siRNA lipid nanoparticles for the treatment of KRAS-mutant tumors
Authors: Shubaash Anthiya, Süleyman Can Öztürk, Hamdullah Yanik, Ece Tavukcuoglu, Adem Şahin, Dhrubajyoti Datta, Klaus Charisse, David Moreira Álvarez, María Isabel Loza, Alfonso Calvo, Einar Sulheim, Simon Loevenich, Geir Klinkenberg, Ruth Schmid, Muthiah Manoharan, Güneş Esendağlı, Maria Jose Alonso
Journal: Journal of Controlled Release (2023)

K-RAS is a highly relevant oncogene that is mutated in approximately 90% of pancreatic cancers and 20-25% of lung adenocarcinomas. The aim of this work was to develop a new anti-KRAS siRNA therapeutic strategy through the engineering of functionalized lipid nanoparticles (LNPs). To do this, first, a potent pan anti-KRAS siRNA sequence was chosen from the literature and different chemical modifications of siRNA were tested for their transfection efficacy (KRAS knockdown) and anti-proliferative effects on various cancer cell lines. Second, a selected siRNA candidate was loaded into tLyp-1 targeted and non-targeted lipid nanoparticles (LNPs). The biodistribution and antitumoral efficacy of selected siRNA-loaded LNP-prototypes were evaluated in vivo using a pancreatic cancer murine model (subcutaneous xenograft CFPAC-1 tumors). Our results show that tLyp-1-tagged targeted LNPs have an enhanced accumulation in the tumor compared to non-targeted LNPs. Moreover, a significant reduction in the pancreatic tumor growth was observed when the anti-KRAS siRNA treatment was combined with a classical chemotherapeutic agent, gemcitabine. In conclusion, our work demonstrates the benefits of using a targeting approach to improve tumor accumulation of siRNA-LNPs and its positive impact on tumor reduction.
Reply: Hepatic steatosis and glycemic burden in chronic hepatitis B
Authors: Lung-Yi Mak, Man-Fung Yuen, Wai-Kay Seto
Journal: Hepatology (2023)

1Department of Medicine, School of Clinical Medicine 2State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong Financial support statement: Not available Correspondence Wai-Kay Seto, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Pokfulam Road 102, Hong Kong. Email: [email protected] This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/
Evolutionary Trajectories are Contingent on Mitonuclear Interactions
Authors: Damien Biot-Pelletier, Stefano Bettinazzi, Isabelle Gagnon-Arsenault, Alexandre K Dubé, Camille Bédard, Tuc H M Nguyen, Heather L Fiumera, Sophie Breton, Christian R Landry
Journal: Molecular Biology and Evolution (2023)

Abstract Critical mitochondrial functions, including cellular respiration, rely on frequently interacting components expressed from both the mitochondrial and nuclear genomes. The fitness of eukaryotic organisms depends on a tight collaboration between both genomes. In the face of an elevated rate of evolution in mtDNA, current models predict that the maintenance of mitonuclear compatibility relies on compensatory evolution of the nuclear genome. Mitonuclear interactions would therefore exert an influence on evolutionary trajectories. One prediction from this model is that the same nuclear genome evolving with different mitochondrial haplotypes would follow distinct molecular paths toward higher fitness. To test this prediction, we submitted 1,344 populations derived from 7 mitonuclear genotypes of Saccharomyces cerevisiae to &amp;gt;300 generations of experimental evolution in conditions that either select for a mitochondrial function or do not strictly require respiration for survival. Performing high-throughput phenotyping and whole-genome sequencing on independently evolved individuals, we identified numerous examples of gene-level evolutionary convergence among populations with the same mitonuclear background. Phenotypic and genotypic data on strains derived from this evolution experiment identify the nuclear genome and the environment as the main determinants of evolutionary divergence, but also show a modulating role for the mitochondrial genome exerted both directly and via interactions with the two other components. We finally recapitulated a subset of prominent loss-of-function alleles in the ancestral backgrounds and confirmed a generalized pattern of mitonuclear-specific and highly epistatic fitness effects. Together, these results demonstrate how mitonuclear interactions can dictate evolutionary divergence of populations with identical starting nuclear genotypes.
The Menstrual Cup
Authors: Joelle Natalie Mouhanna, Judith Simms-Cendan, Sabrina Pastor-Carvajal
Journal: JAMA (2023)

This JAMA Insights in the Women’s Health series aims to expand clinician knowledge about the safety and best practices of menstrual cup use to support patients who choose this product by discussing the advantages, insertion and removal process, and potential risks of menstrual cup use.
The relevance of the circadian timing system role in patients with HIV/AIDS: a quick glance
Authors: Maryam Shafaati, Khosro Sadeghniiat, None Priyanka, Arezu Najafia, Milad Zandi, Samaneh Akbarpour, Om Prakash Choudhary
Journal: International Journal of Surgery (2023)

Shafaati, Maryam PhD; Sadeghniiat, Khosro MD; Priyanka, PhD; Najafia, Arezu MD; Zandi, Milad PhD; Akbarpour, Samaneh PhD; Choudhary, Om Prakash PhD Author Information
Intestinal bacteria and colorectal cancer: etiology and treatment
Authors: Michael W. Dougherty, Christian Jobin
Journal: Gut Microbes (2023)

The etiology of colorectal cancer (CRC) is influenced by bacterial communities that colonize the gastrointestinal tract. These microorganisms derive essential nutrients from indigestible dietary or host-derived compounds and activate molecular signaling pathways necessary for normal tissue and immune function. Associative and mechanistic studies have identified bacterial species whose presence may increase CRC risk, including notable examples such as Fusobacterium nucleatum, Enterotoxigenic Bacteroides fragilis, and pks+ E. coli. In recent years this work has expanded in scope to include aspects of host mutational status, intra-tumoral microbial heterogeneity, transient infection, and the cumulative influence of multiple carcinogenic bacteria after sequential or co-colonization. In this review, we will provide an updated overview of how host-bacteria interactions influence CRC development, how this knowledge may be utilized to diagnose or prevent CRC, and how the gut microbiome influences CRC treatment efficacy.
Association of Household Opioid Availability With Opioid Overdose
Authors: Michelle A. Hendricks, Sanae El Ibrahimi, Grant A. Ritter, Diana Flores, Michael A. Fischer, Roger D. Weiss, Dagan A. Wright, Scott G. Weiner
Journal: JAMA Network Open (2023)

Importance Previous studies that examined the role of household opioid prescriptions in opioid overdose risk were limited to commercial claims, did not include fatal overdoses, and had limited inclusion of household prescription characteristics. Broader research is needed to expand understanding of the risk of overdose. Objective To assess the role of household opioid availability and other household prescription factors associated with individuals’ odds of fatal or nonfatal opioid overdose. Design, Setting, and Participants A retrospective cohort study assessing patient outcomes from January 1, 2015, through December 31, 2018, was conducted on adults in the Oregon Comprehensive Opioid Risk Registry database in households of at least 2 members. Data analysis was performed between October 16, 2020, and January 26, 2023. Exposures Household opioid prescription availability and household prescription characteristics. Main Outcomes and Measures Opioid overdoses were captured from insurance claims, death records, and hospital discharge data. Household opioid prescription availability and prescription characteristics for individuals and households were modeled as 6-month cumulative time-dependent measures, updated monthly. To assess the association between household prescription availability, household prescription characteristics, and overdose, multilevel logistic regression models were developed, adjusting for demographic, clinical, household, and prescription characteristics. Results The sample included 1 691 856 individuals in 1 187 140 households, of which most were women (53.2%), White race (70.7%), living in metropolitan areas (75.8%), and having commercial insurance (51.8%), no Elixhauser comorbidities (69.5%), and no opioid prescription fills in the study period (57.0%). A total of 28 747 opioid overdose events were observed during the study period (0.0526 per 100 person-months). Relative to individuals without personal or household opioid fills, the odds of opioid-related overdose increased by 60% when another household member had an opioid fill in the past 6 months (adjusted odds ratio [aOR], 1.60; 95% CI, 1.54-1.66) and were highest when both the individual and another household member had opioid fills in the preceding 6 months (aOR, 6.25; 95% CI, 6.09-6.40). Conclusions and Relevance In this cohort study of adult Oregon residents in households of at least 2 members, the findings suggest that household prescription availability is associated with increased odds of opioid overdose for others in the household, even if they do not have their own opioid prescription. These findings underscore the importance of educating patients about proper opioid disposal and the risks of household opioids.